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Q&A: How argenx’s CEO plans to create a sequel to Vyvgart (and beat the IRA)

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Tim Van Hauwermeiren is one of Europe’s most successful biotech entrepreneurs, having turned a €1 million investment crisis into a drug company worth more than $28 billion today.

The Dutch company’s sole commercial drug, the FcRN inhibitor Vyvgart, is approved for three immune conditions and is being tested in a dozen more, drawing comparisons to mega-blockbuster Humira.

Now the company hopes to replicate that pipeline-in-a-product model with new drugs. At the company’s R&D day this week, Van Hauwermeiren said Vyvgart’s potential is so large that argenx is working on successors to the molecule — partly in response to the Inflation Reduction Act, which will allow the US government to lower the drug’s high price once it’s been on the market for 13 years.

Endpoints News spoke to Van Hauwermeiren about how the IRA is influencing argenx’s strategy and the company’s push to find its next blockbuster medicine. The interview has been substantially edited for length and clarity.

Ryan Cross: What do you think about the balance between pushing what you can do with Vyvgart versus starting to shift some resources to other potential products?

Tim Van Hauwermeiren: We’re doing all of it. We’re not prioritizing. In 2019, we promised that by 2025 we will be in 15 indications for Vyvgart. We’re already there. For empasiprubart, the next molecule, we’re already in four indications. And for ARGX-119 we’re already in three indications.

Cross: I’m guessing the pressure is on to replicate what you’ve done with Vyvgart?

Van Hauwermeiren: This is where the next-gen Vyvgart comes into play. A simple analogy would be Novo Nordisk in diabetes. Novo has been able to build multiple generations of innovation. That’s what we will do. But you need more to build a great company. The standard cannot be that, to make it into the argenx pipeline, you need to be the next Vyvgart. That’s a once-in-a-lifetime drug.

Cross: Some of your targets beyond FcRN already appear to have pipeline-in-a-product potential. Is that a requirement?

Van Hauwermeiren: We’re not going to develop a technology for the sake of developing technology and then go after the same old targets. I’m sick and tired of HER2, HER3, CD19, CD20. The world needs new biology.

Now, if you take on new biology, which is pretty risky, you’d better be very thoughtful. The biology should be relevant for more than one indication. That is an absolute requirement.

Cross: You emphasized a couple of times today that the opportunity around FcRN is too big for one drug. Are there things Vyvgart can’t do? Or is this about patents and the Inflation Reduction Act?

Van Hauwermeiren: Vyvgart is a hell of a molecule. The problem is, the clock is ticking. The IRA will hit 13 years after the first launch, whether you like it or not. And you know what the IRA is going to do? It’s going to be dramatically reducing your price.

Cross: So are you going to start clinical trials for more diseases with Vyvgart? Or will you save those for the successor drug ARGX-213?

Van Hauwermeiren: That’s a business debate happening currently within argenx. The list is longer than the 15 indications. We have really exciting opportunities still in front of us.

But we need to figure out how fast we can run the Phase 3 clinical trial and still earn a reasonable return. Or will we, for example, do a Phase 2 proof-of-concept with Vyvgart and then hand the baton to the next-gen drug, which starts a whole new clock? These are the interesting business discussions which we’re currently having.

Cross: You’re being quite forthright about this as a company. You’re saying, let’s actually make a whole new molecule, not just a tiny tweak, not just a patent thicket around Vyvgart, but a whole new molecule.

Van Hauwermeiren: It has to be, Ryan. It will have to be a molecule that is distinct, significantly different and better. Otherwise, the payer will simply say, “No, we will, we will stick with Vyvgart, thank you.”

What we tried to showcase today on the podium is that ARGX-213, which is the first of several successors to Vyvgart, can replace four weekly infusions of Vyvgart with single administration. It was multi-years of work.

Cross: But how confident are you that you’re going to be able to make something that is substantially better, and not just more convenient?

Van Hauwermeiren: Job number one is to create the optionality. This molecule also binds to albumin. There is literature suggesting that if you can traffic on albumin, you have an advantage in biodistribution because albumin is sucked into spots of inflammation. So we’re going to see whether there is extra mileage in this molecule.

Cross: In terms of the spirit of what the IRA is trying to do in terms of bringing drug pricing down, are you worried about how this move might be perceived as just a way to get around that?

Van Hauwermeiren: No, not at all. I don’t think it’s the first time that people dramatically improve on original concepts. We have seen how people moved to bispecific antibodies or antibody-drug conjugates going after similar targets. It’s a natural evolution. Look at the Novo example, for diabetes.

Cross: I want to ask a few questions about specific conditions you’re working on, starting with Sjögren’s disease. It’s quickly becoming a pretty competitive area. (Johnson and Johnson reported positive Phase 2 data of a similar drug in June.)

Van Hauwermeiren: This is a big market, right? It occurs in 1 in 1000 people. It’s a space that badly needs innovation. What we’re trying to do today is show how bad a disease can be, because investors just don’t realize it. This space will support multiple innovative molecules.

Cross: Really briefly on ARGX-119, which you’re going to start testing in ALS later this year. The drug activates a protein called MuSK, which helps cluster receptors vital for communicating between nerves and muscles. It’s a really interesting idea, but so many drugs in ALS haven’t worked. Why did you decide to get into that space?

Van Hauwermeiren: We’re currently working on three indications for ARGX-119. Simplistically, one indication, congenital myasthenic syndrome, is low-risk, low-reward. There are not many patients, so it’s a smaller opportunity. But from a biological point of view, it’s the cleanest shot on goal we can place.

ALS is on the other end of the spectrum. It’s high-risk, high reward. In ALS, the first step is that the nerve and the muscle cells start to disconnect. I think we’ll show that by activating MuSK, you can actually stimulate the system to stay connected longer. It’s totally additive to anything else people are developing. It works in the preclinical models. Now we’re going to test it in patients.

Cross: Thank you for your time.

Van Hauwermeiren: Thank you.


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